发生慢性移植肾功能不全者以西罗莫司替换环孢素A的临床疗效

The outcomes in renal allograft recipients after conversion from cyclosporine A to sirolimus for chronic renal allograft dysfunction

目的对采用以环孢素A（CsA）为基础免疫抑制剂的慢性移植肾功能不全（CRAD）患者，将CsA转换为西罗莫司（SRL），观察转换后的临床效果和安全性。方法20例肾移植后出现CRAD的患者，采用突然转换法将CsA替换为SRL（3mg／d），霉酚酸酯（MMF）和泼尼松（Pred）的剂量维持不变。另随机选取9例仍然使用CsA、MMF和Pred的CRAD患者作为对照。观察血肌酐（Cr）、肾小球滤过率（GFR）和24h尿蛋白定量的变化情况以及SRL的不良反应。结果对照组与转换组在患者年龄、性别构成比、移植后时间、转换时的血Cr水平和转换时免疫抑制剂用量等方面的差异均无统计学意义。随访1年，转换组有18例完成观察，其中11例（61．1％，11／18）转换有效，7例（38．9％，1／18）转换无效。转换有效者和转化无效者在转换时的血Cr、移植后时间、GFR及24h尿蛋白定量等方面的差异有统计学意义。转换有效者的血Cr明显下降，GFR明显升高，而转换无效者的血Cr呈进行性升高，GFR呈进行性下降。转换治疗期间，1例出现急性排斥反应，经冲击治疗后逆转。完成随访的18例中，2例发生感染，3例出现皮疹，3例出现腹泻，2例出现口腔溃疡，8例出现骨髓抑制，6例转氨酶升高，10例出现高血脂，4例出现低血钾，没有患者因为上述不良反应而退出观察。结论肾移植后采用以CsA为基础的免疫抑制方案者，若出现CRAD，可以将CsA替换为SRL，部分患者的肾功能得到改善，但转换应在移植肾功能发生严重损害前进行。

Objective To investigate the efficacy and the safety of conversion from cyclosporine A to sirolimus in management of chronic renal allograft dysfunction in kidney allograft recipients. Methods Twenty kidney recipients with chronic renal allograft dysfunction underwent abrupt cessation of cyclosporine A and sirolimus addition, meanwhile the doses of mycophenolate mofetil and prednisolone remained unchanged. Nine cases were randomly identified as the control group. Serum creatinine, glomerular filtration rate （GFR）, 24-h urine protein and the adverse events associated with sirolimus were analyzed. Results There were no significant differences in age, gender, the transplant duration and pre-conversion immunosuppressants between the conversion group and the control group. After follow-up for 12 months, 18 patients in the conversion group completed the study. Among the 18 patients,11 （61. 1%） were identified with improved or stable serum creatinine and GFR, while 7 （38.9 %） with progressive deterioration of serum creatinine and GFR. The analysis showed significant difference in serum creatinine, GFR, the transplant duration and 24-h urine protein at conversion between the successful conversion group and the invalid conversion group. One patient experienced acute rejection episode, and was alleviated with the impulse of bulk methylprednisolone. Among the 18 patients,infection （2/18）, rash （3/18）, diarrhea （3/18）, dental ulcer （2/18）, myelosuppression （8/18）,increased transaminase （6/18）, hyperlipemia （10/18） and hypopotassemia （4/18） were observed and no one exited the study because of the above adverse effects. Conclusion The conversion from cyelosporine A to sirolimus is recommended in kidney transplant recipients with chronic allograft dysfunction, who received eyclosporine A-based immunosuppression protocol before the conversion, and some may get much benefit from the conversion, but the conversion should be performed before the deterioration of allograft function is too far advanced.